Imipramine's selective suppression of an L-type calcium channel in neurons of murine dorsal root ganglia involves G proteins.

The whole cell recording technique was used to explore the depressant effect of the tricyclic antidepressant imipramine (IP) on calcium currents of neurons in cultures of murine dorsal root ganglia. The maximal whole cell current (ICa) mediated by the L-type calcium channel declined to 54% of control within 3 min of superfusing neurons with a solution containing 30 microM IP. In contrast, the T-type calcium current was unchanged. The IP-induced reduction of ICa was not associated with a change of the current-voltage relations of ICa. The depressant effect of IP on ICa was greatly reduced if neurons were pretreated with pertussis toxin or dialyzed with an intracellular solution containing guanosine 5'-O-2-thiodiphosphate. In contrast, superfusion of neurons with 5 mM 8-bromo-cyclic-AMP did not alter the effect of IP upon ICa. These data suggest that the selective suppressant effect of IP on the L-type calcium channel involves either an interaction with that region of the channel complex coupled to guanosine nucleotide-binding proteins or with guanosine nucleotide-binding proteins themselves.